It is known that a compound represented by general formula (VI-a): ##STR3##
(wherein R.sup.1 represents a hydrogen atom or an alkali metal) [hereinafter referred to as Compound (VI-a)] or the lactone form of Compound (VI-a) represented by general formula (VI-b): ##STR4##
[hereinafter referred to as Compound (VI-b)] inhibits HMG-CoA reductase and exhibits the activity to lower the serum cholesterol level, etc. [The Journal of Antibiotics, 29, 1346 (1976)].
Some microorganisms are known to have the ability to convert a compound represented by general formula (V-a): ##STR5##
(wherein R.sup.1 represents a hydrogen atom or an alkali metal) [hereinafter referred to as Compound (V-a)] or the lactone form of Compound (V-a) represented by general formula (V-b): ##STR6##
[hereinafter referred to as Compound (V-b)] into Compound (VI-a) or Compound (VI-b). Such microorganisms include those belonging to the genus Absidia, Cunninghamella, Syncephalasporum or Streptomyces (Japanese Published Unexamined Patent Application No. 50894/82), those belonging to the genus Actinomucor, Circinella, Gongronella, Mortierella, Mucor, Phycomyces, Rhyzopus, Syncephalastrum, Zygorhynchus, Pycnoporus, Rhizoctonia or Nocardia [The Journal of Antibiotics, 36, 887 (1983)], those belonging to the genus Amycolata, Saccharopolyspora, Amycolatopsis or Saccharothrix (Japanese Published Unexamined Patent Application No. 184670/95) and those belonging to the genus Actinomadura (WO96/40863).
The above microorganisms belong to actinomycetes or filamentous fungi. So far, there has not been known a microorganism which belongs to bacteria and has the ability to convert Compound (V-a) or Compound (V-b) into Compound (VI-a) or Compound (VI-b), respectively, like those of the present invention. Actinomycetes and filamentous fungi have the drawback that their growth rate is lower than that of bacteria and thus more time is required for obtaining enough cells for the reaction. Further, there is the problem of controlling the culturing of actinomycetes and filamentous fungi in a fermenter. As actinomycetes and filamentous fungi grow by elongating hyphae, the viscosity of the culture rises as they grow in a fermenter. This often causes shortage of oxygen and makes the culture unhomogenous, which will lower the efficiency of reaction. To solve this problem of oxygen shortage and keep the culture homogenous, the stirring rate of the fermenter must be raised; but hyphae are liable to be cut by stirring at a higher rate, which will lower the activity of microorganisms [Fundamentals of Fermentation Technology, p. 169-190, P. F. Stansbury, A. Whitakaer, Gakkai Shuppan Center (1988)]. Culturing of actinomycetes and filamentous fungi involves such problems. On the other hand, culturing of bacteria, which do not form hyphae, can be readily carried out because the viscosity of the culture hardly rises, and insufficiency of aeration and lack of homogeneity of the culture are seldom observed.
In the DNA recombination technology, expression of genes in bacteria such as Escherichia coli is commonly carried out. However, it is generally difficult to efficiently express genes of actinomycetes and filamentous fungi because their codon usage are widely different from those of bacteria such as Escherichia coli.
The available tools for efficient expression of genes in actinomycetes, such as vectors and promoters are limited. Therefore, it is desirable to employ bacteria, in which various vectors, promoters, etc. can be used, in order to express genes at a high level and to carry out reactions more efficiently. Any genes from bacteria can be readily expressed in bacteria at a high level.